Document Detail


GABA synthesis in Schwann cells is induced by the neuroactive steroid allopregnanolone.
MedLine Citation:
PMID:  19943853     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent evidence showed that neurotransmitters are synthesised in glial cells, such as the Schwann cells, which form myelin sheaths in the PNS. While the presence of GABA type A (GABA-A) receptors has been previously demonstrated in these cells, the evidence of GABA synthesis remained still elusive. In an attempt to demonstrate the presence of GABA in rat Schwann cells, we adopted a strategy, using several integrated neurochemical, molecular as well as immunocytochemical approaches. We first demonstrated the presence of glutamic acid decarboxylase of 67 kDa (GAD67) in Schwann cells, a crucial enzyme of the GABA synthesis mechanism. Second, we demonstrated that GABA is synthesized and localized in Schwann cells. As the third step we showed that allopregnanolone (10 nM), a potent allosteric modulator of GABA-A receptors, stimulates GABA synthesis through increased levels of GAD67 in Schwann cells. Analysis of intracellular signalling mechanisms revealed that the protein kinase A pathway, through enhanced cAMP levels and cAMP response element binding protein phosphorylation, modulates the allosteric action of allopregnanolone at the GABA-A receptor in Schwann cells. Our findings are the first to demonstrate that this GABA mechanism is active in Schwann cells thus establishing new potential therapeutic targets to control Schwann cell biology, which may prove useful in the treatment of several neurodegenerative disorders.
Authors:
Valerio Magnaghi; Arpad Parducz; Angelisa Frasca; Marinella Ballabio; Patrizia Procacci; Giorgio Racagni; Giambattista Bonanno; Fabio Fumagalli
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-27
Journal Detail:
Title:  Journal of neurochemistry     Volume:  112     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-09     Completed Date:  2010-03-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  980-90     Citation Subset:  IM    
Affiliation:
Department of Endocrinology, Physiopathology and Applied Biology, Universit? degli Studi di Milano, Milan, Italy.
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MeSH Terms
Descriptor/Qualifier:
Anesthetics / pharmacology*
Animals
CREB-Binding Protein / metabolism
Cells, Cultured
Chromatography, High Pressure Liquid / methods
Computational Biology / methods
Cyclic AMP / metabolism
Forskolin / pharmacology
Gene Expression Regulation / drug effects*
Glutamate Decarboxylase / genetics,  metabolism
Phosphorylation / drug effects
Pregnanolone / pharmacology*
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Schwann Cells / drug effects*,  metabolism
Sciatic Nerve / cytology
Signal Transduction / drug effects
Time Factors
Up-Regulation
gamma-Aminobutyric Acid / metabolism*
Chemical
Reg. No./Substance:
0/Anesthetics; 0/RNA, Messenger; 128-20-1/Pregnanolone; 56-12-2/gamma-Aminobutyric Acid; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; EC 2.3.1.48/CREB-Binding Protein; EC 4.1.1.15/Glutamate Decarboxylase; EC 4.1.1.15/glutamate decarboxylase 1; EC 4.1.1.15/glutamate decarboxylase 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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